Rifampicin preparation

A number of oxime derivatives of rifaldehyde have been prepared. Many of these derivatives exhibit good activity against rifampicin-resistant organisms (151,152). 

By using in vitro preparations of human enzymes it is possible to predict those antibiotics that will adversely affect the metabolism of other drugs [110]. Such studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/ml, did not inhibit human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 [34], In an in vitro hepatocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4) [34], an isoenzyme which rifampicin is known to induce [109],... 

Several hundred semisynthetic derivatives have been prepared in an effort to obtain substances with better biological activities (for references see Ref.s)). Particularly positions 3 and 4 of the naphthoquinone ring system (numbering system as proposed by Prelog7 8) have been extensively substituted, since it has been shown that structural changes in these two positions do not critically affect the action of the substance on the target enzyme, the bacterial RNA polymerase (cf. Chapter 3.). They can, however, influence other parameters such as its ability to penetrate into cells, its pharmacokinetic properties and resorption, which are all important for clinical use as an antibiotic. Rifampicin (U.S. rifampin), which is a widely used orally active tuberculostatic agent, is a 3-(4-methyl piperazinyl)-iminomethyl derivative of rifamycin SV, synthesized via the 3-formyl derivative (Fig. 5)10 ... 

Dissolve 10 mg rifampicin (rifamycin SV) in 1.0 ml dimethyl sulfoxide. Prepare also a 5% (w/v) solution of trichloroacetic acid (TCA). 3-107. Place exactly 0.1 ml H-leucine solution (step 3-105) in a 125 ml Erlenmeyer flask and place the flask in the bath. 

At 13 minutes after initiation of the experiment, transfer 2.5 ml of the culture to a second 125 ml flask containing 0.05 ml of the rifampicin solution prepared in step 3-106. Mix the solution thoroughly. 

Sesame oil may be used as a solvent in the preparation of subcutaneous injections, oral capsules, rectal suppositories, and ophthalmic preparations it may also be used in the formulation of suspensions and emulsions. Multiple-emulsion formulations, in which sesame oil was one of the oil phases incorporated, have been investigated as a prolonged-release system for rifampicin microemulsions containing sesame oil have been prepared for the transdermal delivery of ketoprofen. Sesame oil has also been used in the preparation of liniments, pastes, ointments, and soaps. A sesame paste... 

A semi-synthetic antibiotic, rifampicin (rifampin) (19), was prepared from compound 5, obtained by the formylation of the C-3 position of rifamycin SV (3), followed by the reaction of 5 with l-amino-4-methylpiperazine in tetrahydrofuran (Fig. 2) [69]. 

Ober, C.A., Kalombo, L., Swai, H., and Gupta, R.B. Preparation of rifampicin/lactose microparticle composites by a supercritical antisolvent-drug excipient mixing technique for inhalation delivery. 

Doan TV, Olivier JC. Preparation of rifampicin-loaded PLGA microspheres for lung delivery as aerosol by premix membrane homogenization. International Journal of Pharmaceutics. December 1, 2009 382(l-2) 61-66. PubMed PMID 19682562. 

A stable multiple emulsion containing rifampicin (92) in the internal aqueous phase was prepared by the incorpo-... 

Rifamycins B and O can be transformed into rifamycin S, and rifamycin SV is obtained by treating rifamycin S with ascorbic acid [5]. Formylation of the C3 position of rifamycin SV, followed by the combination of this alkaloid with l-amino-4-methylpiperazine, gave the semisynthetic ansamy-cin rifampicin. Rifampicin was prepared in 1966, and it is one of the most effective antituberculosis agents at present. The chemical structures of the rifamycins were finally clarified in 1973-1974 [6,7]. 

Another controversial point is the inhibition of mitochondial DNA-dependent RNA polymerases by rifampicin. Several reports state that the mitochondrial enzyme is rather insensitive to this inhibitor, in either intact mitochondria or solubilized mitochondrial preparations (Winters-... 

Liang Y-D, Song J-F, Xu M (2007) Electrochemiluminescence from successive electro- and chemo-oxidation of rifampicin and its application to the determination of rifampicin in pharmaceutical preparations and human urine. Spectrochim Acta, Part A 67(2) 430-436. doi 10.1016/j.saa.2006.07.036... 

An alginate-based nanoparticulate delivery system was developed for frontline antituberculosis dmgs (rifampicin, isoniazid, pyrazinamide and ethambutol). Alginate nanoparticles were prepared by controlled cation-induced gelification and administered orally to mice. The drug levels were analysed by high performance liquid chromatography (HPLC) in plasma and tissues. The therapeutic efficacy was... 

Fig. 4. The time dependence of cell-free enzyme synthesis uninhibited and inhibited at varying times by actinomycin or rifampicin. Synthesis was carried out as described in Table 1 except for the following modifications. In the control experiment, samples were removed from the synthesis system and assayed at the times indicated on the abscissa. In the actinomycin and rifampicin experiments, the inhibitor (2 jitg of actinomycin or 1 ju,g of rifampicin per milliliter) was added at the time indicated on the abscissa, and the incubation was continued for another 60 minutes before assay. All values have been normalized to an assay time of 200 minutes. The S-30 used was prepared from strain 514 which contains a deletion of the entire lac region including the repressor gene.

Yudkin [86] offered evidence that the messenger half-life for penicillinase differed in induced and constitutive mutant strains of B. licheniformis 749, based on penicillinase synthesis after treatment with actinomycin. In induced cultures the half-life was about 2 to 3 minutes, while in the constitutive mutant the half-hfe appeared to be 10 minutes. Yudkin [87] did not obtain similar results with other constitutive strains, and this high value is therefore not substantiated. Davies [84,88], using both actinomycin and rifampicin, inferred messenger half-lives of about 4.7 minutes for both induced and constitutive penicillinase synthesis. Subsequent experiments (Davies and Collins, in preparation) have given shorter estimates of 2 to 4 minutes for penicillinase messenger half-life during vanadate-induced synthesis. 

It was found that the macrocyclic ring of rifamycin was responsible for the complex formation of the antibiotic with E. coli RNA polymerase and for the inhibitory effect of the antibiotic on the enzyme. Changes in other parts of the molecule have little effect on the direct action on E. coli RNA polymerase but may affect its permeability characteristics . Some derivatives of rifamycin, prepared by substitution with cyclic secondary amines, displayed activity against rifampicin resistant mutants of Staphylococcus aureus . ... 

Recently we attempted to prepare monosize PLA particles in micron size range as carriers for potential colloidal drug delivery formulations. We prepared PLA particles in a wide size range of 1-50 im by a conventional solvent evaporation method and its modified form. A tuberculostatic drug (i.e., rifampicin) was loaded in these particles. Here, the preparation procedure, the results of drug loading and release experiments of PLA are briefly presented. Details of these studies can be found elsewhere (90,91). 

Ito F, Makino K. 2004. Preparation and properties of monodispersed rifampicin-loaded poly(lactide-co-glycolide) microspheres. Colloids Surf B 39 17-21. 

Calcium ions were also employed in the preparation of rifampicin-containing GL hydrogel for the treatment of osteoarticular tuberculosis (Xue et al., 2012]. 

Rifamycins - Prom lunong the scores of semisynthetic rifamycins prepared from rifamycin SV (XV) and its 3-formyl derivative (XVI), Rifampicin (rifaldazine) (XVII)stands out as a dramatic chemotherapeutic improvement over the parent compound. ... 

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